Indomethacin Tocolysis 

Doyle NM, Gardner MO, Wells L, et al.  Outcome of Very Low Birth Weight Infants Exposed to Antenatal Indomethacin for Tocolysis.  Journal of Perinatology (May 2005) 25: 336-340.

OBJECTIVE: Our purpose is to compare the outcomes of very low birth weight infants who were exposed to antenatal indomethacin with those who were not exposed to this therapy.    

STUDY DESIGN: We used our center's component of the NICHD Neonatal Research Network's Generic Data Base which recorded the outcomes of all live born infants weighing less than 1500 g over a 5-year period. We abstracted data concerning neonatal morbidity (death, Grades III to IV intraventricular hemorrhage (IVH), necrotizing enterocolitis and patent ductus arteriosus), as well as other factors including gestational age, birth weight, antenatal corticosteroid treatment and maternal hypertension or pre-eclampsia. Univariate analysis was performed using Fisher's exact test. Multivariate analysis using logistic regression was performed to control for confounding factors.      
   
RESULTS: A total of 85 infants who were exposed to antenatal indomethacin were compared to 464 infants who were not exposed to the drug. In the univariate analysis, antenatal indomethacin exposure was not associated with a significant increase in the incidence of necrotizing enterocolitis or patent ductus arteriosus. The incidence of Grades III to IV IVH was 17.9% in those infants exposed to antenatal indomethacin compared to 7.1% in the nonexposed infants (p=0.008). The incidence of neonatal death in the exposed infants was 27.7 versus 16.4 in the nonexposed infants (p=0.02). After controlling for antenatal corticosteroids, maternal pre-eclampsia, gestational age and birth weight, antenatal indomethacin was significantly associated with an increased incidence of IVH, but not neonatal death.

CONCLUSION: Antenatal indomethacin was associated with significantly higher rates of IVH. Additional studies assessing the potential risks of indomethacin tocolysis are needed before it is used as a first-line tocolytic therapy.

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Comment.  Although this is only a retrospective review, the data should suggest caution in using indomethacin for tocolysis pending further studies.  There are at least 2 potential mechanisms whereby antenatal indomethacin could promote IVH in preterm infants: 1) bu producing significant flucuations in cerebral blood flow associated with fetal ductal constriction, and 2) by inhibiting platelet function.  ABK.